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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Rhomboid-like	0	DIRECT
Integrin alpha N-terminal domain	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
MIR domain	0	DIRECT
Second domain of FERM	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Sema domain	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
PreATP-grasp domain	0	DIRECT
Mob1/phocein	0	DIRECT
Serpins	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Smc hinge domain	0	DIRECT
ADC-like	0	DIRECT
Plexin repeat	0	DIRECT
Cytokine	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
RCC1/BLIP-II	0	DIRECT
Cdc48 domain 2-like	0	DIRECT
TIMP-like	0	DIRECT
Integrin domains	0	DIRECT
L27 domain	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
SMAD MH1 domain	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
SAP domain	0	DIRECT
cAMP-binding domain-like	0	DIRECT
SAICAR synthase-like	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Putative DNA-binding domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
PX domain	0	DIRECT
ARID-like	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
Homeodomain-like	0.00000000002918	DIRECT
beta-beta-alpha zinc fingers	0.000005788	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00005717	DIRECT
Immunoglobulin	0.0003995	DIRECT
Fibronectin type III	0.000827	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.005638	INHERITED FROM: region of integument || adult external thorax
Protein kinase-like (PK-like)	0.007161	INHERITED FROM: photoreceptor cell R8 of pale ommatidium || intestinal stem cell || adult midgut epithelium
Nuclear receptor ligand-binding domain	0.01023	INHERITED FROM: mushroom body gamma-lobe || supraesophageal ganglion neuron || adult MBp lineage neuron || mushroom body || synaptic neuropil || neuropil || adult MBp lineage clone || protocerebrum || synaptic neuropil block
p53-like transcription factors	0.01023	INHERITED FROM: adult external thorax || mesothoracic tergum
SH2 domain	0.01056	INHERITED FROM: adult peripheral nervous system || photoreceptor cell R7 || ommatidium || midline crossing tract || wing blade
HMG-box	0.04207	INHERITED FROM: adult external thorax || wing
Orange domain-like	0.06431	INHERITED FROM: EL neuron || EG neuron || 5-6I of thorax
EGF/Laminin	0.07374	INHERITED FROM: ocellus || tendon cell || embryonic precursor cell of adult midgut || ventral nervous system || embryonic/larval midgut cell || eye photoreceptor cell stalk || proventriculus || wing blade
Cystine-knot cytokines	0.08812	INHERITED FROM: embryonic/larval posterior spiracle || stigmatophore || embryonic/larval spiracle
Ankyrin repeat	0.1101	INHERITED FROM: Johnston organ neuron
vWA-like	0.1492	INHERITED FROM: endocuticular specialization || muscle attachment site
Transducin (alpha subunit), insertion domain	0.1965	INHERITED FROM: eo neuron
Snake toxin-like	0.1965	INHERITED FROM: embryonic/larval neuromuscular junction || wing cell || wing vein
Toll/Interleukin receptor TIR domain	0.1965	INHERITED FROM: ventral nerve cord
Growth factor receptor domain	0.3014	INHERITED FROM: ocellus || embryonic fiber tract || RP2sib neuron || embryonic/larval midline of ventral nerve cord || surface associated glial cell || dMP2 neuron || wing vein L4 || integumentary specialisation || retinal pigment cell || ventral nervous system || photoreceptor cell R7 || ocellar triangle || ventral midline || proventriculus || wing vein L2 || vMP2 neuron || hindgut || articulation
dsRNA-binding domain-like	0.32	INHERITED FROM: uniglomerular antennal lobe projection neuron || antennal lobe projection neuron adPN || persistent antennal lobe projection neuron || alpha/beta Kenyon cell || Kenyon cell || mushroom body extrinsic neuron || antennal lobe projection neuron iPN || unilateral ACT relay interneuron
(Phosphotyrosine protein) phosphatases II	0.3469	INHERITED FROM: lobe system of adult mushroom body || intersegmental nerve || medial lobe of adult mushroom body
Cytochrome P450	0.3802	INHERITED FROM: embryonic/larval foregut || neuropil glial sheath || embryonic/larval hindgut || midline glial cell || neuropil associated CNS glial cell || commissure || CNS glial cell || midline crossing tract || tract || hindgut || tract neuropil || midgut
SET domain	0.4504	INHERITED FROM: haltere || metathoracic leg
BAR/IMD domain-like	0.4734	INHERITED FROM: neuromuscular junction || NMJ bouton
HAD-like	0.4734	INHERITED FROM: rhabdomere of eye photoreceptor cell
Cadherin-like	0.5306	INHERITED FROM: photoreceptor cell R4
Spectrin repeat	0.5306	INHERITED FROM: longitudinal connective || ipsilateral tract || copper cell || midgut enterocyte || middle midgut || tract || connective

Family domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
NF-kappa-B/REL/DORSAL transcription factors, C-terminal domain	0	DIRECT
PX domain	0	DIRECT
Phosphatidylinositol phosphate kinase IIbeta, PIPK IIbeta	0	DIRECT
ARID domain	0	DIRECT
Integrin alpha N-terminal domain	0	DIRECT
Mob1/phocein	0	DIRECT
Eps15 homology domain (EH domain)	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Dachshund-homology domain	0	DIRECT
Arrestin/Vps26-like	0	DIRECT
SPRY domain	0	DIRECT
Transforming growth factor (TGF)-beta	0	DIRECT
Pepsin-like	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase UCH-L	0	DIRECT
Single strand DNA-binding domain, SSB	0	DIRECT
POU-specific domain	0	DIRECT
Synaptotagmin-like (S variant)	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Phosphate binding protein-like	0	DIRECT
Reprolysin-like	0	DIRECT
cAMP-binding domain	0	DIRECT
Plexin repeat	0	DIRECT
Cdc48 domain 2-like	0	DIRECT
Third domain of FERM	0	DIRECT
Choline/Carnitine O-acyltransferase	0	DIRECT
Integrin domains	0	DIRECT
SAP domain	0	DIRECT
Rhomboid-like	0	DIRECT
Phoshoinositide 3-kinase (PI3K) helical domain	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Second domain of FERM	0	DIRECT
MIR domain	0	DIRECT
Extracellular domain of cell surface receptors	0	DIRECT
Fibroblast growth factors (FGF)	0	DIRECT
Laminin-type module	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase, UCH	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Phoshoinositide 3-kinase (PI3K), catalytic domain	0	DIRECT
Sema domain	0	DIRECT
SMAD MH1 domain	0	DIRECT
RNase III catalytic domain-like	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
L-arabinose binding protein-like	0	DIRECT
Serpins	0	DIRECT
First domain of FERM	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Diacylglycerol kinase-like	0	DIRECT
Class II glutamine amidotransferases	0	DIRECT
L27 domain	0	DIRECT
Forkhead DNA-binding domain	0	DIRECT
Cell cycle control phosphatase, catalytic domain	0	DIRECT
Smc hinge domain	0	DIRECT
p120GAP domain-like	0	DIRECT
Rel/Dorsal transcription factors, DNA-binding domain	0	DIRECT
Myb/SANT domain	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
Erythroid transcription factor GATA-1	0	DIRECT
Homeodomain	0.0000000000002018	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.0001008	DIRECT
Fibronectin type III	0.001206	INHERITED FROM: leg taste bristle || nerve || prothoracic leg sensillum || dendritic arborizing neuron || prothoracic leg taste bristle chemosensory neuron || LNv neuron || synaptic neuropil || commissure || LN period neuron || prothoracic leg taste bristle || s-LNv neuron || tract neuropil || adult brain || gustatory receptor neuron
Classic zinc finger, C2H2	0.005029	INHERITED FROM: region of integument
Protein kinases, catalytic subunit	0.00521	INHERITED FROM: photoreceptor cell R8 of pale ommatidium || intestinal stem cell
Nuclear receptor ligand-binding domain	0.01085	INHERITED FROM: mushroom body gamma-lobe || supraesophageal ganglion neuron || adult MBp lineage neuron || mushroom body || synaptic neuropil || neuropil || adult MBp lineage clone || protocerebrum || synaptic neuropil block
SH2 domain	0.01208	INHERITED FROM: adult peripheral nervous system || photoreceptor cell R7 || ommatidium || midline crossing tract || wing blade
Nuclear receptor	0.02639	INHERITED FROM: mushroom body gamma-lobe || supraesophageal ganglion neuron || adult MBp lineage neuron || mushroom body || adult MBp lineage clone || synaptic neuropil block
HMG-box	0.04363	INHERITED FROM: adult external thorax || wing
Paired domain	0.06247	INHERITED FROM: EL neuron || EG neuron || RP2 motor neuron
Higher-molecular-weight phosphotyrosine protein phosphatases	0.06247	INHERITED FROM: intersegmental nerve
Ngr ectodomain-like	0.06247	INHERITED FROM: intersegmental nerve branch ISNb of A1-7 || intersegmental nerve of A1-7 || abdominal intersegmental nerve
Hairy Orange domain	0.08248	INHERITED FROM: EL neuron || EG neuron
I set domains	0.08501	INHERITED FROM: neuropil glial sheath || leg taste bristle || prothoracic leg sensillum || dendritic arborizing neuron || prothoracic leg taste bristle chemosensory neuron || LNv neuron || adult cerebral ganglion || synaptic neuropil || connective || segmental subdivision of organ system || interface glial cell || prothoracic leg taste bristle || s-LNv neuron || tract neuropil || synaptic neuropil block || supraesophageal ganglion || antennal lobe glomerulus || adult brain || gustatory receptor neuron
Histone lysine methyltransferases	0.1092	INHERITED FROM: haltere || metathoracic leg
Ankyrin repeat	0.1302	INHERITED FROM: Johnston organ neuron || ventral multidendritic neuron
PLC-like (P variant)	0.1431	INHERITED FROM: mesothoracic tergum || dorsal multidendritic neuron || dorsal multidendritic neuron ddaC
BTB/POZ domain	0.1609	INHERITED FROM: prothoracic leg
Toll/Interleukin receptor TIR domain	0.189	INHERITED FROM: ventral nerve cord
Transducin (alpha subunit), insertion domain	0.189	INHERITED FROM: eo neuron
SMAD domain	0.2499	INHERITED FROM: wing vein || wing blade || gut section
SAM (sterile alpha motif) domain	0.2729	INHERITED FROM: metatarsus of male prothoracic leg || prothoracic metatarsus || prothoracic tarsal segment || sex comb || mesothoracic leg || metatarsus
Ubiquitin activating enzymes (UBA)	0.3293	INHERITED FROM: protocerebrum
Cytochrome P450	0.3879	INHERITED FROM: embryonic/larval foregut || neuropil glial sheath || embryonic/larval hindgut || midline glial cell || neuropil associated CNS glial cell || commissure || CNS glial cell || midline crossing tract || tract || hindgut || tract neuropil || midgut
Cyclin	0.4176	INHERITED FROM: tagmatic subdivision of organ system
Calponin-homology domain, CH-domain	0.4244	INHERITED FROM: abdominal segmental nerve
EGF-type module	0.4521	INHERITED FROM: embryonic precursor cell of adult midgut || ventral nervous system || embryonic/larval midgut cell || proventriculus || hindgut || wing blade || articulation || adult external head
Growth factor receptor domain	0.4578	INHERITED FROM: ocellus || dorsocentral bristle || integumentary specialisation || ocellar triangle || salivary gland || proventriculus || hindgut
Spectrin repeat	0.5374	INHERITED FROM: longitudinal connective || ipsilateral tract || copper cell || midgut enterocyte || middle midgut || tract || connective
BAR domain	0.6093	INHERITED FROM: NMJ bouton
Cadherin	0.6241	INHERITED FROM: photoreceptor cell R4 || outer photoreceptor cell
G proteins	0.6292	INHERITED FROM: wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
cAMP-binding domain-like	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
TIMP-like	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
SAICAR synthase-like	0	DIRECT
L27 domain	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
SAP domain	0	DIRECT
ARID-like	0	DIRECT
Mob1/phocein	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
ADC-like	0	DIRECT
Serpins	0	DIRECT
Sema domain	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
PX domain	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Cdc48 domain 2-like	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
SMAD MH1 domain	0	DIRECT
Second domain of FERM	0	DIRECT
Integrin alpha N-terminal domain	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Plexin repeat	0	DIRECT
PreATP-grasp domain	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Integrin domains	0	DIRECT
Putative DNA-binding domain	0	DIRECT
Smc hinge domain	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
RCC1/BLIP-II	0	DIRECT
Rhomboid-like	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
MIR domain	0	DIRECT
Cytokine	0	DIRECT
Homeodomain-like	0.00000000002027	DIRECT
beta-beta-alpha zinc fingers	0.000004068	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00004045	DIRECT
Immunoglobulin	0.000282	DIRECT
Fibronectin type III	0.0005806	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.004062	INHERITED FROM: adult external thorax || region of integument
Protein kinase-like (PK-like)	0.005204	INHERITED FROM: adult midgut epithelium || photoreceptor cell R8 of pale ommatidium || intestinal stem cell
p53-like transcription factors	0.00749	INHERITED FROM: mesothoracic tergum || tract || integumentary process || adult external thorax
Nuclear receptor ligand-binding domain	0.00749	INHERITED FROM: neuropil || supraesophageal ganglion neuron || adult MBp lineage clone || mushroom body gamma-lobe || mushroom body || synaptic neuropil || synaptic neuropil block || adult MBp lineage neuron || protocerebrum
SH2 domain	0.007747	INHERITED FROM: connective || adult peripheral nervous system || wing blade || ommatidium || photoreceptor cell R7 || midline crossing tract
HMG-box	0.0326	INHERITED FROM: wing || adult external thorax
Orange domain-like	0.05112	INHERITED FROM: nervous system of embryonic/larval thorax || 5-6I of thorax || EG neuron || EL neuron
EGF/Laminin	0.05913	INHERITED FROM: tendon cell || embryonic precursor cell of adult midgut || wing blade || embryonic/larval midgut cell || eye photoreceptor cell stalk || proventriculus || ocellus || larval caeca region || ventral nervous system
Cystine-knot cytokines	0.07162	INHERITED FROM: embryonic/larval posterior spiracle || embryonic/larval spiracle || stigmatophore || spiracle
Ankyrin repeat	0.09089	INHERITED FROM: Johnston organ neuron
vWA-like	0.1256	INHERITED FROM: endocuticular specialization || muscle attachment site
GTPase activation domain, GAP	0.126	INHERITED FROM: abdominal intersegmental nerve
Transducin (alpha subunit), insertion domain	0.169	INHERITED FROM: eo neuron
Snake toxin-like	0.169	INHERITED FROM: embryonic/larval neuromuscular junction || wing cell || adult optic lobe || wing vein
Toll/Interleukin receptor TIR domain	0.169	INHERITED FROM: ventral nerve cord
Growth factor receptor domain	0.2683	INHERITED FROM: surface associated glial cell || fascicle || articulation || ocellar triangle || integumentary specialisation || wing vein L4 || retinal pigment cell || hindgut || embryonic/larval midline of ventral nerve cord || vMP2 neuron || dMP2 neuron || ventral midline || wing vein L2 || proventriculus || photoreceptor cell R7 || embryonic fiber tract || RP2sib neuron || ocellus || ventral nervous system
dsRNA-binding domain-like	0.286	INHERITED FROM: mushroom body extrinsic neuron || antennal lobe projection neuron adPN || alpha/beta Kenyon cell || antennal lobe projection neuron iPN || Kenyon cell || persistent antennal lobe projection neuron || unilateral ACT relay interneuron || uniglomerular antennal lobe projection neuron
(Phosphotyrosine protein) phosphatases II	0.3128	INHERITED FROM: lobe system of adult mushroom body || intersegmental nerve || medial lobe of adult mushroom body
Cytochrome P450	0.3462	INHERITED FROM: neuropil glial sheath || commissure || neuropil associated CNS glial cell || tract neuropil || embryonic/larval foregut || midline glial cell || midgut || embryonic/larval hindgut || hindgut || tract || CNS glial cell || midline crossing tract
Calponin-homology domain, CH-domain	0.3756	INHERITED FROM: abdominal segmental nerve
SET domain	0.4167	INHERITED FROM: haltere || metathoracic leg
HAD-like	0.4398	INHERITED FROM: rhabdomere || rhabdomere of eye photoreceptor cell
BAR/IMD domain-like	0.4398	INHERITED FROM: NMJ bouton || neuromuscular junction
Cadherin-like	0.4974	INHERITED FROM: photoreceptor cell R4
Spectrin repeat	0.4974	INHERITED FROM: connective || middle midgut || copper cell || longitudinal connective || tract || midgut enterocyte || ipsilateral tract

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
54236,47031 54236 - Ubiquitin-like 47031 - Second domain of FERM	0	DIRECT
57716,48508 57716 - Glucocorticoid receptor-like (DNA-binding domain) 48508 - Nuclear receptor ligand-binding domain	0	DIRECT
81660,56784 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like	0	DIRECT
57903,57903 57903 - FYVE/PHD zinc finger 57903 - FYVE/PHD zinc finger	0	DIRECT
47220,47220 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like	0	DIRECT
52058,52058 52058 - L domain-like 52058 - L domain-like	0	DIRECT
49265,49265 49265 - Fibronectin type III 49265 - Fibronectin type III	0	DIRECT
48425,50729 48425 - Sec7 domain 50729 - PH domain-like	0	DIRECT
52440,56059 52440 - PreATP-grasp domain 56059 - Glutathione synthetase ATP-binding domain-like	0	DIRECT
52058,48726 52058 - L domain-like 48726 - Immunoglobulin	0	DIRECT
101912,103575 101912 - Sema domain 103575 - Plexin repeat	0	DIRECT
50044,55550 50044 - SH3-domain 55550 - SH2 domain	0	DIRECT
69318,69179 69318 - Integrin alpha N-terminal domain 69179 - Integrin domains	0	DIRECT
49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
50692,54585 50692 - ADC-like 54585 - Cdc48 domain 2-like	0	DIRECT
47031,50729 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
69179,69179 69179 - Integrin domains 69179 - Integrin domains	0	DIRECT
47413,46689 47413 - lambda repressor-like DNA-binding domains 46689 - Homeodomain-like	0	DIRECT
57903,47370 57903 - FYVE/PHD zinc finger 47370 - Bromodomain	0	DIRECT
49417,81296 49417 - p53-like transcription factors 81296 - E set domains	0	DIRECT
51206,51206 51206 - cAMP-binding domain-like 51206 - cAMP-binding domain-like	0	DIRECT
48371,56112 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
48403,48403 48403 - Ankyrin repeat 48403 - Ankyrin repeat	0	DIRECT
49562,48371 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat	0	DIRECT
55550,50044 55550 - SH2 domain 50044 - SH3-domain	0	DIRECT
52777,52777 52777 - CoA-dependent acyltransferases 52777 - CoA-dependent acyltransferases	0	DIRECT
55550,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
51045,51045 51045 - WW domain 51045 - WW domain	0	DIRECT
47769,47769 47769 - SAM/Pointed domain 47769 - SAM/Pointed domain	0	DIRECT
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.00001214	DIRECT
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.005998	INHERITED FROM: central nervous system || prothoracic leg taste bristle || tract neuropil || connective || leg taste bristle || LNv neuron || s-LNv neuron || synaptic neuropil || synaptic neuropil block || adult cerebral ganglion || adult brain || antennal lobe glomerulus || prothoracic leg taste bristle chemosensory neuron
48726,49265 48726 - Immunoglobulin 49265 - Fibronectin type III	0.0247	INHERITED FROM: neuropil glial sheath || neuropil associated CNS glial cell || prothoracic leg taste bristle || tract neuropil || connective || lobe system of adult mushroom body || leg taste bristle || LNv neuron || gustatory receptor neuron || s-LNv neuron || prothoracic leg sensillum || giant fiber neuron || adult antennal lobe glomerulus || antennal lobe glomerulus || prothoracic leg taste bristle chemosensory neuron
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0.05112	INHERITED FROM: nervous system of embryonic/larval thorax || 5-6I of thorax || EG neuron || EL neuron
49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0.06921	INHERITED FROM: peripheral nervous system || photoreceptor cell R4
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.169	INHERITED FROM: articulation || scutum || integumentary specialisation || inner photoreceptor cell || joint || leg || wing vein || proventriculus || photoreceptor cell R7 || intersegmental nerve || wing blade dorsal compartment
47895,52540 47895 - Transducin (alpha subunit), insertion domain 52540 - P-loop containing nucleoside triphosphate hydrolases	0.169	INHERITED FROM: eo neuron
47459,55785 47459 - HLH, helix-loop-helix DNA-binding domain 55785 - PYP-like sensor domain (PAS domain)	0.169	INHERITED FROM: sclerite
81296,81296 81296 - E set domains 81296 - E set domains	0.2285	INHERITED FROM: abdominal segmental nerve || segmental nerve || abdominal intersegmental nerve || abdominal nerve || intersegmental nerve
46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat	0.303	INHERITED FROM: tract neuropil || connective || middle midgut || copper cell || longitudinal connective || tract || midgut enterocyte || ipsilateral tract
50156,50044 50156 - PDZ domain-like 50044 - SH3-domain	0.3064	INHERITED FROM: embryonic/larval peripheral nervous system
52799,52799 52799 - (Phosphotyrosine protein) phosphatases II 52799 - (Phosphotyrosine protein) phosphatases II	0.3064	INHERITED FROM: embryonic/larval peripheral nervous system || nerve || abdominal segmental nerve || segmental nerve || abdominal nerve || intersegmental nerve
57184,57196 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0.3791	INHERITED FROM: integumentary specialisation
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.3963	INHERITED FROM: articulation || secondary pigment cell || ocellar triangle || frons || eye photoreceptor cell stalk || joint || postfrons || tertiary pigment cell || proventriculus || intersegmental nerve branch ISNb of A1-7 || ocellus || wing blade dorsal compartment || ventral nervous system
49313,49313 49313 - Cadherin-like 49313 - Cadherin-like	0.5857	INHERITED FROM: wing hair || photoreceptor cell R4 || outer photoreceptor cell

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
57196,49899,49899 57196 - EGF/Laminin 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
49562,48371,56112 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
52058,52058,52058 52058 - L domain-like 52058 - L domain-like 52058 - L domain-like	0	DIRECT
49899,49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
69318,69179,69179 69318 - Integrin alpha N-terminal domain 69179 - Integrin domains 69179 - Integrin domains	0	DIRECT
54236,47031,50729 54236 - Ubiquitin-like 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
81660,56784,81665 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like 81665 - Calcium ATPase, transmembrane domain M	0	DIRECT
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0	DIRECT
57667,57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.0001544	DIRECT
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.03865	INHERITED FROM: commissure || prothoracic leg taste bristle || tract neuropil || connective || leg taste bristle || LNv neuron || gustatory receptor neuron || s-LNv neuron || synaptic neuropil || adult cerebral ganglion || adult brain || adult antennal lobe glomerulus || antennal lobe glomerulus || prothoracic leg taste bristle chemosensory neuron
48726,48726,49265 48726 - Immunoglobulin 48726 - Immunoglobulin 49265 - Fibronectin type III	0.05521	INHERITED FROM: neuropil glial sheath || neuropil associated CNS glial cell || prothoracic leg taste bristle || tract neuropil || connective || lobe system of adult mushroom body || leg taste bristle || LNv neuron || gustatory receptor neuron || s-LNv neuron || embryonic/larval central nervous system || prothoracic leg sensillum || giant fiber neuron || adult antennal lobe glomerulus || antennal lobe glomerulus || prothoracic leg taste bristle chemosensory neuron
57196,57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin 57196 - EGF/Laminin	0.1178	INHERITED FROM: photoreceptor cell R1 || articulation || secondary pigment cell || ocellar triangle || frons || adult peripheral nervous system || eye photoreceptor cell stalk || photoreceptor cell R6 || joint || postfrons || gut section || tertiary pigment cell || proventriculus || adult external head || ocellus || wing blade dorsal compartment || ventral nervous system
46966,46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat 46966 - Spectrin repeat	0.169	INHERITED FROM: connective || middle midgut || copper cell || longitudinal connective || tract || midgut enterocyte || ipsilateral tract
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.2285	INHERITED FROM: scutum || integumentary specialisation || nerve || mesothoracic tergum || adult external mesothorax || tergum || intersegmental nerve || dorsal mesothorax
49313,49313,49313 49313 - Cadherin-like 49313 - Cadherin-like 49313 - Cadherin-like	0.5857	INHERITED FROM: wing hair || photoreceptor cell R4 || outer photoreceptor cell

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.